F2RL1
F2RL1, also known as PAR2, GPR11 or proteinase-activated receptor 2, is a cell surface G protein-coupled receptor for trypsin and trypsin-like enzymes. It links extracellular proteolysis to inflammatory, immune and vascular signalling. Browse Assay Genie's current range of F2RL1 research reagents below, or read on for the biology behind the target.
F2RL1 is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus acts as a tethered ligand that binds an extracellular loop domain of the receptor. Signalling runs through several pathways, including phospholipase C, intracellular calcium, MAPK, I-kappaB kinase/NF-kappaB and Rho. The receptor associates with a subset of G protein alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, and it can also be transactivated by cleaved F2R/PAR1. It is believed to be a class B receptor that internalises as a complex with arrestin and traffics to endosomal vesicles. Beta-arrestin scaffolds also support cytoskeletal rearrangement and chemotaxis through cofilin dephosphorylation.
F2RL1 acts as a sensor for proteolytic enzymes generated during infection and generally promotes inflammation. It can signal synergistically with TLR4 and probably TLR2, and it modulates TLR3 signalling. It is involved in leukocyte recruitment and is the major PAR receptor able to modulate eosinophil function. During inflammation it promotes dendritic cell maturation, trafficking to lymph nodes and subsequent T-cell activation. Activation enhances phagocytosis of Gram-positive bacteria and killing of Gram-negative bacteria, and the receptor acts synergistically with interferon-gamma in antiviral responses. In vascular biology, activation lowers blood pressure, probably through vasodilation, and it has a protective role in the endothelial barrier involving coagulation factor X. In airway epithelium it has been proposed to be bronchoprotective, yet it can also compromise the barrier by interrupting E-cadherin adhesion.
The F2RL1 gene belongs to the G protein-coupled receptor 1 family and the HGNC F2R receptors group. Its previous name was coagulation factor II (thrombin) receptor-like 1. The receptor is implicated in acute and chronic inflammatory diseases of the joints, lungs, brain, gastrointestinal tract, periodontium, skin and vascular systems, and in autoimmune disorders. Mouse and rat orthologues are both named F2rl1.
F2RL1 generally promotes inflammation and is implicated in inflammatory diseases of the joints, lungs, brain, gut, periodontium, skin and vasculature.
The receptor senses proteases produced during infection, regulates dendritic cell maturation and eosinophil function, and enhances antibacterial and antiviral responses.
Activation promotes vascular smooth muscle relaxation and lowers blood pressure, while F2RL1 also supports endothelial barrier integrity involving coagulation factor X.
Tethered-ligand activation, G protein coupling, beta-arrestin scaffolds and NF-kappaB, MAPK and JNK signalling make F2RL1 a useful model for protease-driven GPCR biology.
F2RL1 is a G protein-coupled receptor activated by trypsin and trypsin-like proteases through cleavage of its amino terminus. It signals through PLC, calcium, MAPK, NF-kappaB and Rho pathways, modulating inflammation, innate and adaptive immunity, and vascular tone.
F2RL1 is also called PAR2, GPR11 and proteinase-activated receptor 2. Its previous HGNC name was coagulation factor II (thrombin) receptor-like 1, and the current name is F2R like trypsin receptor 1. It sits in the F2R receptors gene group.
Mouse and rat both carry an orthologous F2rl1 gene. In human, the receptor is implicated in acute and chronic inflammatory diseases affecting the joints, lungs, brain, gastrointestinal tract, periodontium, skin and vascular systems, and in autoimmune disorders. Check the datasheet of any product for its validated reactivity.
Other protease-activated receptors, Toll-like receptors, coagulation factors and signalling partners linked to F2RL1 biology.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P55085; product specifications from Assay Genie datasheets.